Lectins are proteins that bind to specific carbohydrate structures and can thus recognize particular glycoconjugates. Galectins are a family of over 10 structurally related lectins that bind beta-galactosides.
Galectin-3 is a 26 kDa beta-galactoside-binding protein belonging to the galectin family. This protein is composed of a carboxyl-terminal carbohydrate-recognition domain (CRD) and amino-terminal tandem repeats. Galectin-3 is found in epithelia of many organs, as well as in various inflammatory cells, including macrophages, dendritic cells and Kupffer cells. The expression of galectin-3 is upregulated during inflammation, cell proliferation, cell differentiation, and through transactivation by viral proteins. Its expression is also affected by neoplastic transformation—upregulated in certain types of lymphomas and thyroid carcinoma; downregulated in other types of malignancies, such as colon, breast, ovarian and uterine carcinomas. Recently, it has been reported that the expression of this lectin has a strong correlation with the grade and malignant potential of primary brain tumors. Increased galectin-3 expression has also been noted in human atherosclerotic lesions. These findings suggest that galectin-3 may mediate both physiological and pathological responses.
Galectin-3 has been shown to function through both intracellular and extracellular actions. Related to its intracellular functions, galectin-3 has been identified as a component of hnRNP, a factor in pre-mRNA splicing. Intracellular galectin-3 has also been found to exert cell cycle control and prevent T cell apoptosis, the latter probably mediated through interaction with the Bcl-2 family members. Extracellular forms of galectin-3 secreted from monocytes/macrophages and epithelial cells, function in the activation of various types of cells, including monocytes/macrophages, mast cells, neutrophils, and lymphocytes. Galectin-3 has also been shown to mediate cell-cell and cell-extracellular matrix interactions.
Galectin-9, another member of the galectin family with two CRDs, is a selective chemoattractant for eosinophils. The activity requires both CRDs, suggesting that cross-linking of cell surface molecules is involved in the chemoattraction. Galectin-3 is known to form dimers through the amino-terminal non-lectin domain and thus has the potential to cross-link appropriate cell surface glycoproteins.
Extracellularly, galectin-3 is known to bind to the cell surfaces of monocytes/macrophages. High levels of galectin-3 expression are seen in human and rat lungs, where macrophages are one of the dominant cell types. Moreover, the recruitment of macrophages during peritonitis has been found to be attenuated in galectin-3-deficient mouse.